Lower Expression of Nrdp1 in Human Glioma Contributes Tumor Progression by Reducing Apoptosis
Lower Expression of Nrdp1 in Human Glioma Contributes Tumor Progression by Reducing Apoptosis
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人神经胶质瘤中 Nrdp1 的低表达通过减少细胞凋亡促进肿瘤进展
DOI：
10.1002/iub.1320
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发表时间：
2014-10-01
期刊：
影响因子：
4.6
通讯作者：
Yu, Rutong
中科院分区：
文献类型：
--
作者：
Shi, Hengliang;Du, Jin;Yu, Rutong
泛素连接酶Nrdp 1（neuregulin receptor degradation protein 1）是一种重要的蛋白质，它可以泛素化多种底物，如ErbB 3、布鲁斯、MyD 88、C/EBP β和Parkin等。除了生理功能外，它还被发现参与肿瘤进展。研究表明，Nrdp 1的缺失会促进乳腺癌细胞的生长。Nrdp 1在胶质瘤中的作用至今尚未阐明。在此，我们报道了Nrdp 1和切割的caspase 3在人脑胶质瘤组织中的表达低于非肿瘤组织。然后我们发现Nrdp 1和切割的caspase 3的表达在替莫唑胺（TMZ）治疗胶质瘤化疗药物的治疗中增加。进一步研究表明，瞬时转染Nrdp 1可通过加重布鲁斯降解和caspase 3激活，显著促进细胞凋亡。此外，Nrdp 1过表达通过评估布鲁斯的降解和caspase 3的激活来增强TMZ诱导的凋亡，而Nrdp 1沉默通过抑制人脑胶质瘤细胞中布鲁斯的降解和caspase 3的激活来降低对TMZ的敏感性。这些观察结果表明，Nrdp 1是一个促凋亡蛋白在人脑胶质瘤和Nrdp 1的低表达可能会促进肿瘤的进展，通过减少凋亡，这表明Nrdp 1可能是一个重要的调节人胶质瘤的发展。(C)2014 IUBMB Life，66（10）：704-710，2014
Ubiquitin ligase Nrdp1 (neuregulin receptor degradation protein 1) plays important roles in multiple physiological process because it can ubiquitinate various substrates such as ErbB3, BRUCE, MyD88, C/EBP beta, and Parkin, and so forth. In addition to the physiological function, it was also found to be involved in tumor progression. It has been shown that loss of Nrdp1 enhances breast cancer cell growth. Up to now, the role of Nrdp1 in glioma has not been elucidated. Here, we reported that Nrdp1 as well as cleaved caspase 3 was lower expressed in human glioma tissues comparing with the nontumorous. And then we found that the expression of Nrdp1 and cleaved caspase 3 was increased in the treatment of Temozolomide (TMZ), a drug for glioma chemotherapy. Further investigation indicated that transient transfection of Nrdp1 significantly promoted cell apoptosis by aggravating the degradation of BRUCE and activation of caspase 3. In addition, overexpression of Nrdp1 augmented TMZ induced apoptosis by evaluating the degradation of BRUCE and the activation of caspase 3, while silencing of Nrdp1 reduced the sensitivity to the TMZ by inhibiting the degradation of BRUCE and the activation of caspase 3 in human glioma cells. These observations show that Nrdp1 is a pro-apoptotic protein in human glioma and lower expression of Nrdp1 in human glioma may promote tumor progression by reducing apoptosis, suggesting that Nrdp1 may be an important regulator in the development of human glioma. (C) 2014 IUBMB Life, 66(10): 704-710, 2014